TSEAC Meeting - 8/1/11

The Food and Drug Administration (FDA) sought advice from the Transmissible Spongiform Encephalopathies Advisory Committee on whether individuals who have spent time in Saudi Arabia should be deferred as blood donors or ineligible as human cell, tissue, and cellular- and tissue-based product donors (HCT/Ps) to reduce the risk of variant Creutzfeldt-Jakob Disease (vCJD), transmission. David Asher, MD, Office of Blood Research and Review, FDA, presented the vCJD issue and the history of vCJD in the United Kingdom (U.K.) and the description of the three vCJD cases attributed to exposure to the bovine spongiform encephalopathy (BSE), agent in Saudi Arabia.

Michael B. Coulthart, Ph.D., Public Health Agency of Canada, described the most recent vCJD case from March 2011. The individual was a recent immigrant who spent most of his early life (1986-1998) in Saudi Arabia. The diagnosis of vCJD was supported by results of a tonsil biopsy. Canadian authorities concluded that the man, who has no history of surgery or blood transfusion, was probably infected by dietary exposure to the BSE agent while in the Arabian Peninsula, most likely in Saudi Arabia.

The other two cases were described by Dr. Asher. One case was diagnosed by a brain biopsy and occurred in a person living in Virginia who was a non Saudi Arabian national, born and raised in Saudi Arabia. The third case also was diagnosed by a brain biopsy. The affected individual may have visited France; however, it was concluded that he most likely was infected in Saudi Arabia.

Saudi Arabia has not reported any case of BSE to the World Organization for Animal Health. However, live cattle and beef products were imported from the U.K. during the period of concern (1980-1996), and Saudi Arabia was identified as a consignee of meat-and-bone meal (MBM), of U.K. origin, during the years when MBM might have been contaminated with the BSE agent (1988-1993).

Melissa Greenwald, MD, Office of Cellular Tissue and Gene Therapies, FDA presented current criteria for screening HCT/P donors for vCJD risk. Greenwald noted that the HCT/P donor screening recommendations do not exclude donors for exposure to injected bovine insulin and do not distinguish between France and the rest of Europe, as do the criteria for whole blood and/or source plasma donors. A difficulty with this and all risk exposures is that donor medical history interviews, when the donor is deceased, are performed by questioning someone other than the donor.

Luisa Gregori, PhD, OBRR, presented the history of the current vCJD deferral criteria. FDA's recommendations regarding deferral of blood donors and the ineligibility of donors of HCT/Ps potentially exposed to the BSE agent involve geographic deferrals based on rough comparisons of the estimated risk of oral exposure to the BSE agent in various groups of people compared to the risk of oral exposure to the BSE agent in the U.K. population from the beginning of 1980 until the end of 1996, when U.K. food/feed protections were fully implemented. In 2001, FDA announced a model that estimated the risk in most countries of Western Europe assigned as a relative-risk compared to the risk in the U.K. The risk of dietary exposure to the BSE agent was assumed to be directly related to the time spent in a country where the BSE agent contaminated the product. The following relative risks were assigned: U.K.=1.0, France=0.05 and other countries of Western Europe=0.015. A risk relative to U.K. of 0.35 was assigned to U.S. military bases in Europe that obtained beef from the U.K.

Potential Consumption of U.K. Beef Products by Persons Residing in Saudi Arabia, 1980-1996

When calculating the risk of dietary exposure to the BSE agent, FDA considered: 1) estimated U.K. exports of beef to Saudi Arabia and 2) estimated total beef consumption in Saudi Arabia. Published sources suggested that about 10 percent of beef imported into Saudi Arabia during the years of concern might have originated in the U.K. and that the annual per capita beef consumption in Saudi Arabia was about a quarter of that in the U.K. Therefore, according to the FDA analysis, the average relative risk estimate for dietary exposure to the BSE agent in U.K. beef by persons residing in Saudi Arabia during the years 1980-1996 might be 0.025.

U.S. Military Personnel on Bases in Saudi Arabia

FDA was provided information from the U.S. Department of Defense about sources of beef. Military beef found in field rations "meals ready to eat" during those years was all of U.S. origin. However, an uncertain amount of the beef sold to and consumed by U.S. military personnel living on U.S. bases in Saudi Arabia after 1980 originated in the U.K., though such procurement decreased after 1989. FDA therefore assumed that the risk of dietary exposure to the BSE agent for U.S. military personnel living on bases in Saudi Arabia to be about 35 percent of that for U.K. residents during the same period.

Deferrals of Blood Donors Residing in Saudi Arabia

Dr. Coulthart reported that since November of 2007, Hema-Quebec has requested deferral of blood donors residing in Saudi Arabia for any period of six months or more from 1980 through 1996. Since March 2011, Canadian Blood Services has required the same deferral.

David A. Lincoln, Lt. Col., USAF, BSC, informed the committee that beginning in late August 2011 or early September 2011 the Armed Services Blood Program will implement the same deferral as Canada. Lt. Col. Lincoln noted that the effect of additional donor deferrals on military collections is expected to be limited, as many of the military personnel who were in Saudi Arabia during those years may have retired or left the military.

Open Public Forum

A Saudi government representative reviewed historical measures adopted by Saudi Arabia to prevent importation of BSE-risk products. The representative reported that in 1990 Saudi Arabia instituted a National Ban that barred the importation of live cattle, beef, and cattle byproducts including MBM from BSE countries. Also, in 1990, the Kingdom of Saudi Arabia implemented a heightened surveillance system.

Committee Discussion and Vote

The question posed by the FDA to TSEAC was, "Based on an analogy in Western Europe, do available data support the consideration by FDA to recommend deferring donors of blood and blood components, including Source Plasma, and to determine to be ineligible donors of HCT/Ps who

  1. Spent six months or more cumulatively in Saudi Arabia as U.S. military personnel from the beginning of 1980 through the end of 1996 or
  2. Otherwise spent more than five years cumulatively in Saudi Arabia from the beginning of 1980 through the end of 1996?"

The committee vote for Part a. was 12 yes, 4 no

The committee vote for Part b. was 15 yes, 1 no

Several committee members commented on different aspects such as noting that deferrals based on modeling appear to be unnecessary as enough time has passed to accumulate actual data.

The committee was asked to discuss the likely contribution of these recommendations to the safety of the products involved and the possible impact on supplies of blood, blood components, plasma derivatives and HCT/Ps. A range of comments was provided, including 1) more data are needed for HCT/Ps, 2) the recommendations are more of a precautionary measure because of the uncertainty in the data, but there would likely be a miniscule improvement in safety, and 3) there was no substantive discussion of Source Plasma issues.

The committee was asked to comment on additional information that might better inform FDA's consideration of the proposed or any further safety measures. The committee suggested the FDA revisit the original recommendation from 1999 of vCJD deferrals. The FDA should also work with the Saudi Health authorities to take a closer look at these vCJD cases. The committee suggested that FDA continue to look at other countries where possibly there is either a misdiagnosis of vCJD or no human surveillance for BSE.